Skip to main content
SpringerLink
Log in

Preparation of High-quality Glabridin Extract from Glycyrrhiza glabra

  • Research Paper
  • Bioprocess Engineering
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Supercritical fluid extraction (SFE) using cosolvent-modified supercritical carbon dioxide and a two-step separation/purification method was investigated as a way to improve the purity of glabridin, one of the many bioactive components of Glycyrrhiza glabra (licorice). The SFE parameters were optimized using an analytical-scale SFE system in the temperature range 40–80°C and the pressure range 10–50 MPa. The extraction was then scaled up by 100 times using a preparative SFE system under the following set of optimized conditions: 40°C, 30 MPa, and SCCO2 modified with ethanol equivalent to its 25% (v/v) concentration. The glabridin purity obtained through the scaled-up SFE system was 6.2%, a much higher level than that obtained through organic solvent extraction. The licorice extract obtained by scaling up the SFE system was isolated and purified by applying alcohol precipitation/ filtration and adsorption chromatography with 80% aqueous ethanol to obtain a purer product. It was confirmed that the glabridin purity of the final extract product was increased by up to 37%, without significant loss of glabridin after two separation/purification steps.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kaur, R., H. Kaur, and A. S. Dhindsa (2013) Glycyrrhiza glabra: A Phytopharmacological review. Int. J. Pharm. Sci. Res. 4: 2470–2477.

    Google Scholar 

  2. Fenwick, G. R., J. Lutomski, and C. Nieman (1990) Liquorice, Glycyrrhiza glabra L.- composition, uses and analysis. Food Chem. 38: 119–143.

    Article  CAS  Google Scholar 

  3. Ahn, J., H. Lee, J. Jang, S. Kim, and T. Ha (2013) Anti-obesity effects of glabridin-rich supercritical carbon dioxide extract of licorice in high-fat-fed obese mice. Food Chem. Toxicol. 51: 439–445.

    Article  CAS  PubMed  Google Scholar 

  4. Aoki, F., K. Nakagawa, A. Tanaka, K. Matsuzaki, N. Arai, and T. Mae (2005) Determination of glabridin in human plasma by solid-phase extraction and LC-MS/MS. J. Chromatogr. B 828: 70–74.

    Article  CAS  Google Scholar 

  5. Ito, C., N. Oi, T. Hashimoto, H. Nakabayashi, F. Aoki, Y. Tominaga, S. Yokota, K. Hosoe, and K. Kanazawa (2007) Absorption of dietary licorice isoflavan glabridin to blood circulation in rats. J. Nutr. Sci. Vitaminol. 53: 358–365.

    Article  CAS  PubMed  Google Scholar 

  6. Lim, T. K. (2016) Edible Medicinal and Non-medicinal Plants: Modified Stems, Roots, Bulbs. pp. 354–457. Springer, Dordrecht, Netherlands.

    Google Scholar 

  7. Aviram, M., M. Rosenblat, S. Billecke, J. Erogul, R. Sorenson, C. L. Bisgaier, R. S. Newton, and B. L. Du (1999) Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic. Biol. Med. 26: 892–904.

    Article  CAS  PubMed  Google Scholar 

  8. Belinky, P. A., M. Aviram, S. Mahmood, and J. Vaya (1998) Structural aspects of the inhibitory effect of glabridin on LDL oxidation. Free Radic. Biol. Med. 24: 1419–1429.

    Article  CAS  PubMed  Google Scholar 

  9. Nerya, O., J. Vaya, R. Musa, S. Izrael, R. Ben-Arie, and S. Tamir (2003) Glabrene and isoliquiritigenin as tyrosinase inhibitors from licorice roots. J. Agric. Food Chem. 51: 1201–1207.

    Article  CAS  PubMed  Google Scholar 

  10. Yokota, T., H. Nishio, Y. Kubota, and M. Mizoguchi (1998) The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res. 11: 355–361.

    Article  CAS  PubMed  Google Scholar 

  11. Tamir, S., M. Eizenberg, D. Somjen, S. Izrael, and J. Vaya (2001) Estrogen-like activity of glabrene and other constituents isolated from licorice root. J. Steroid Biochem. Mol. Biol. 78: 291–298.

    Article  CAS  PubMed  Google Scholar 

  12. Ofir, R., S. Tamir, S. Khatib, and J. Vaya (2003) Inhibition of serotonin re-uptake by licorice_constituents. J. Mol. Neurosci. 20: 135–140.

    Article  CAS  PubMed  Google Scholar 

  13. Sawada, K., Y. Yamashita, T. Zhang, K. Nakagawa, and H. Ashida (2014) Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cells. Mol. Cell. Endocrinol. 393: 99–108.

    Article  CAS  Google Scholar 

  14. Nakagawa, K., H. Kishida, N. Arai, T. Nishiyama, and T. Mae (2004) Licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-Ay mice. Biol. Pharm. Bull. 27: 1775–1778.

    Article  CAS  PubMed  Google Scholar 

  15. Lee, J. W., S. S. Choe, H. Jang, J. Kim, H. W. Jeong, H. Jo, K. H. Jeong, S. Tadi, M. G. Park, T. H. Kwak, J. M. Kim, D. H. Hyun, and J. B. Kim (2012) AMPK activation with glabridin ameliorates adiposity and lipid dysregulation in obesity. J. Lipid Res. 53: 1277–1286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Aoki, F., S. Honda, H. Kishida, M. Kitano, N. Arai, H. Tanaka, S. Yokota, K. Nakagawa, T. Asakura, Y. Nakai, and T. Mae (2007) Suppression by licorice flavonoids of abdominal fat accumulation and body weight gain in high-fat diet-induced obese C57BL/6J mice. Biosci. Biotechnol. Biochem. 71: 206–214.

    Article  CAS  PubMed  Google Scholar 

  17. Haraguchi, H., N. Yoshida, H. Ishikawa, Y. Tamura, K. Mizutani, and T. Kinoshita (2000) Protection of mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra. J. Pharm. Pharmacol. 52: 219–223.

    Article  CAS  PubMed  Google Scholar 

  18. Shang, H., S. Cao, J. Wang, H. Zheng, and R. Putheti (2010) Glabridin from Chinese herb licorice inhibits fatigue in mice. Afr. J. Tradit Complement. Altern. Med. 7: 17–23.

    Article  CAS  Google Scholar 

  19. Fukai, T., K. Satoh, T. Nomura, and H. Sakagami (2003) Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra. Fitoterapia. 74: 624–629.

    Article  CAS  PubMed  Google Scholar 

  20. Fukai, T., A. Marumo, K. Kaitou, T. Kanda, S. Terada, and T. Nomura (2002) Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci. 71: 1449–1463.

    Article  CAS  PubMed  Google Scholar 

  21. Simmler, C., G. F. Pauli, and S.-N. Chen (2013) Phytochemistry and biological properties of glabridin. Fitoterapia 90: 160–184.

    Article  CAS  PubMed  Google Scholar 

  22. Pastorino, G., L. Cornara, S. Soares, F. Rodrigues, and M. B. P. P. Oliveira (2018) Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phytother. Res. 32: 2323–2339.

    Article  CAS  PubMed  Google Scholar 

  23. Zadeh, J. B., Z. M. Kor, and M. K. Goftar (2013) Licorice (Glycyrrhiza glabra Linn) as a valuable medicinal plant. Int. J. Adv. Biol. Biomed. Res. 1: 1281–1288.

    CAS  Google Scholar 

  24. Tian, M., H. Yan, and K. Row (2008) Extraction of glycyrrhizic acid and glabridin from licorice. Int. J. Mol. Sci. 9: 571–577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Viswanathan, V., R. Pharande, A. Bannalikar, P. Gupta, U. Gupta, and A. Mukne (2019) Inhalable liposomes of Glycyrrhiza glabra extract for use in tuberculosis: formulation, in vitro characterization, in vivo lung deposition, and in vivo pharmacodynamic studies. Drug Dev. Ind. Pharm. 45: 11–20.

    Article  CAS  PubMed  Google Scholar 

  26. Modarresi, M., Y. Manoochehri, F. Ahmadi, and L. Hosseinzadeh (2017) Protective effects of glabridin against cytotoxicity and oxidative stress induced by doxorubicin in PC12 cells. J. Rep. Pharm. Sci. 6: 1–12.

    Google Scholar 

  27. Da Silva, R. P. F. F., T. A. P. Rocha–Santos, and A. C. Duarte (2016) Supercritical fluid extraction of bioactive compounds. Trends Analyt. Chem. 76: 40–51.

    Article  CAS  Google Scholar 

  28. Durante, M., M. S. Lenucci, and G. Mita (2014) Supercritical carbon dioxide extraction of carotenoids from pumpkin (Cucurbita spp.): A review. Int. J. Mol. Sci. 15: 6725–6740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Patil, P. D., K. P. R. Dandamudi, J. Wang, Q. Deng, and S. Deng (2018) Extraction of bio-oils from algae with supercritical carbon dioxide and co-solvents. J. Supercrit. Fluids 135: 60–68.

    Article  CAS  Google Scholar 

  30. Sajilata, M. G., R. S. Singhal, and M. Y. Kamat (2008) Supercritical CO2 extraction of γ-linolenic acid (GLA) from Spirulina platensis ARM 740 using response surface methodology. J. Food Eng. 84: 321–326.

    Article  CAS  Google Scholar 

  31. Charpe, T. W. and V. K. Rathod (2015) Separation of glycyrrhizic acid from licorice root extract using macroporous resin. Food Bioprod. Process. 93: 51–57.

    Article  CAS  Google Scholar 

  32. Garcia-Vaquero, M., G. Rajauria, J. V. O’Doherty, and T. Sweeney (2017) Polysaccharides from macroalgae: Recent advances, innovative technologies and challenges in extraction and purification. Food Res. Int. 99: 1011–1020.

    Article  CAS  PubMed  Google Scholar 

  33. Xu, Y., Q. Yuan, X. Hou, and Y. Lin (2009) Preparative separation of glabridin from glycyrrhiza glabra L. extracts with macroporous resins. Sep. Sci. Technol. 44: 3717–3734.

    Article  CAS  Google Scholar 

  34. Cho, Y.-K., H.-S. Kim, J.-W. Kim, S.-Y. Lee, W.-S. Kim, J.-H. Ryu, and G.-B. Lim (2004) Extraction of glabridin from licorice using supercritical carbon dioxide. KSBB J. 19: 427–432.

    Google Scholar 

  35. Markom, M., M. Hasan, W. R. W. Daud, H. Singh, and J. M. Jahim (2007) Extraction of hydrolysable tannins from Phyllanthus niruri Linn.: Effects of solvents and extraction methods. Sep. Purif. Technol. 52: 487–496.

    Article  CAS  Google Scholar 

  36. Kim, H.-S., B.-Y. Kim, S.-Y. Lee, W.-S. Kim, E.-K. Lee, J.-H. Ryu, and G.-B. Lim (2003) Extraction of glycyrrhizic acid from licorice using supercritical carbon dioxide/aqueous ethanol. KSBB J. 18: 347–351.

    Google Scholar 

  37. Castro-Vargas, H. I., L. I. Rodríguez-Varela, S. R. S. Ferreira, and F. Parada-Alfonso (2010) Extraction of phenolic fraction from guava seeds (Psidium guajava L.) using supercritical carbon dioxide and co-solvents. J. Supercrit. Fluids 51: 319–324.

    Article  CAS  Google Scholar 

  38. Gañán, N. A., A. M. A. Dias, F. Bombald, J. A. Zygadlo, E. A. Brignole, H. C. de Sousa, and M. E. M. Braga (2016) Alkaloids from Chelidonium majus L.: Fractionated supercritical CO2 extraction with co-solvents. Sep. Purif. Technol. 165: 199–207.

    Article  CAS  Google Scholar 

  39. Tonthubthimthong, P., S. Chuaprasert, P. Douglas, and W. Luewisutthichat (2001) Supercritical CO2 extraction of nimbin from neem seeds - an experimental study. J. Food Eng. 47: 289–293.

    Article  Google Scholar 

  40. Rincón, J., R. Camarillo, and V. Ancillo (2016) Cosolvent effect on the recovery of triglycerides from used frying oil with modified supercritical ethane. J. Supercrit. Fluids 110: 83–89.

    Article  CAS  Google Scholar 

  41. Korea Food & Drug Administration, Licorice extract. https://www.foodsafetykorea.go.kr/foodcode

Download references

Acknowledgement

The paper was supported by The University of Suwon in 2015.

Author information

Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, 03722, Korea

    Jin-Hee Hong, In-IL Jung, Seungjoo Haam & Sang-Yun Lee

  2. Department of Chemical and Biochemical Engineering, The University of Suwon, Hwaseong, 18323, Korea

    Yun-Kyoung Cho, Giobin Lim & Jong-Hoon Ryu

Authors
  1. Jin-Hee Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. In-IL Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yun-Kyoung Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seungjoo Haam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sang-Yun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giobin Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jong-Hoon Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Giobin Lim or Jong-Hoon Ryu.

Additional information

Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hong, JH., Jung, II., Cho, YK. et al. Preparation of High-quality Glabridin Extract from Glycyrrhiza glabra. Biotechnol Bioproc E 24, 666–674 (2019). https://doi.org/10.1007/s12257-019-0121-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-019-0121-7

Keywords

Search

Navigation